PROJECT ABSTRACT This proposal addresses the relationship between depressive symptoms and daily oral pre-exposure prophylaxis (PrEP) use among sub-Saharan African women. Prior research has shown that PrEP is highly efficacious in preventing HIV transmission when adherence is high. This has led to a rapid increase in PrEP delivery projects throughout Africa, but HIV incidence rates remain elevated among young women who have difficulty adhering to the daily drug regimen. Depression is also highly prevalent in the same populations of young women and has been linked to increased HIV risk behaviors and decreased healthcare engagement and ART adherence among HIV-positive individuals. The intersection between depression and adherence has not been well-studied in HIV-negative individuals but depression is hypothesized to be a key factor limiting PrEP's uptake, adherence, and overall effectiveness among high-risk women. This study seeks to address this critical gap in HIV-prevention research by: 1) determining whether depressive symptoms reduce PrEP adherence among HIV-negative women from Kenya and Uganda who participated in a prospective, open-label implementation study of PrEP delivery; 2) investigating the psychosocial and behavioral mechanisms by which depressive symptoms impact PrEP adherence among young women participating in an ongoing, randomized prospective PrEP adherence trial in South Africa and Zimbabwe; and 3) exploring the experiences of HIV- uninfected Kenyan women completing a depressive symptom screening tool in the context of a PrEP delivery intervention. The proposed research will use both quantitative and qualitative methods to provide new evidence on the impact of depressive symptoms on PrEP use among women in these four different sub- Saharan geographies. It will also inform the development of integrated mental health and HIV prevention interventions by providing insight into whether a depressive symptom screening tool can be used to direct enhanced PrEP adherence counseling among high-risk, HIV-negative women in these contexts. Such novel intervention approaches have the potential to improve PrEP effectiveness and reduce the burden of HIV among African women.